The exposure of workers to hot environments is expected to increase as a result of climate change. In order to prevent heat-related illness, it is recommended that workers take breaks during working hours. However, this would lead to reductions in worktime and labor productivity. In this study, we estimate the economic cost of heat-related illness prevention through worker breaks associated with climate change under a wide range of climatic and socioeconomic conditions. We calculate the worktime reduction based on the recommendation of work/rest ratio and the estimated future wet bulb glove temperature, which is an index of heat stresses. Corresponding GDP losses (cost of heat-related illness prevention through worker breaks) are estimated using a computable general equilibrium model throughout this century. Under the highest emission scenario, GDP losses in 2100 will range from 2.6 to 4.0% compared to the current climate conditions. On the other hand, GDP losses will be less than 0.5% if the 2.0 °C goal is achieved. The benefit of climate-change mitigation for avoiding worktime loss is comparable to the cost of mitigation (cost of the greenhouse gas emission reduction) under the 2.0 °C goal. The relationship between the cost of heat-related illness prevention through worker breaks and global average temperature rise is approximately linear, and the difference in economic loss between the 1.5 °C goal and the 2.0 °C goal is expected to be approximately 0.3% of global GDP in 2100. Although climate mitigation and socioeconomic development can limit the vulnerable regions and sectors, particularly in developing countries, outdoor work is still expected to be affected. The effectiveness of some adaptation measures such as additional installation of air conditioning devices or shifting the time of day for working are also suggested. In order to reduce the economic impacts, adaptation measures should also be implemented as well as pursing ambitious climate change mitigation targets.